title: The neuronal protein Kidins220/ARMS associates with ICAM-3 and other uropod components and regulates T-cell motility.
abstract: Kinase D interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is a protein that is mainly expressed in brain and neural cells where its function is only starting to be characterized. Here, we show that Kidins220/ARMS is also expressed in T lymphocytes where it is highly concentrated at the uropod of polarized T cells. In this cellular model, Kidins220/ARMS colocalizes with typical uropod T-cell molecules and coimmunoprecipitates with ICAM-3. Furthermore, Kidins220/ARMS associates with raft domains at the uropod and coimmunoprecipitates with caveolin-1, a molecule we show here to be also expressed in T cells. Importantly, induction of morphological polarization in primary T lymphocytes and Jurkat cells enhances Kidins220/ARMS colocalization with ICAM-3. Conversely, disruption of cell polarity provokes Kidins220/ARMS redistribution from the uropod to other cellular regions and drastically impairs its association with ICAM-3 in a protein kinase C-dependent manner. Finally, Kidins220/ARMS knockdown in human polarized T-cell lines promotes both basal and stromal cell-derived factor-1α-induced directed migration, identifying a novel function for this molecule. Altogether, our findings show that Kidins220/ARMS is a novel component of the uropod involved in the regulation of T-cell motility, an essential process for the immune response.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Roberto Martín
authors.initials: RM
authors.lastname: Jean-Mairet
authors.forename: Celia
authors.initials: C
authors.lastname: López-Menéndez
authors.forename: Lucía
authors.initials: L
authors.lastname: Sánchez-Ruiloba
authors.forename: Sandra
authors.initials: S
authors.lastname: Sacristán
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez-Martínez
authors.forename: Lorena
authors.initials: L
authors.lastname: Riol-Blanco
authors.forename: Paloma
authors.initials: P
authors.lastname: Sánchez-Mateos
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: José Luis
authors.initials: JL
authors.lastname: Rodríguez-Fernández
authors.forename: Miguel R
authors.initials: MR
authors.lastname: Campanero
authors.forename: Teresa
authors.initials: T
authors.lastname: Iglesias
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D051242:Caveolin 1 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D051381:Rats; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051242:Caveolin 1; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; C482591:KIDINS220 protein, human; C544017:Kidins220 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins